1. Field of the Invention
The present invention relates generally to the field of blood clotting research. More specifically, the present invention provides methods of using decorin proteoglycan as an anticoagulating and/or antithrombotic agent to inhibit fibrin(ogen) clot formation.
2. Description of the Related Art
Decorin is composed of a 40 kDa core protein and a glycosaminoglycan chain. Many glycosaminoglycans affect blood coagulation activity. For example, heparin and heparan sulfate have been used as efficient anticoagulants clinically for decades. These polysaccharides indirectly inhibit thrombin by activating serpins. Heparin activates antithrombin III, the major physiological regulator of thrombin, as well as heparin cofactor II. Both heparin-induced thrombocytopenia and hemorrhage are side effects to the use of heparin as an antithrombotic agent.
Although heparin/antithrombin III complexes efficiently inhibit soluble thrombin, they only weakly inhibit thrombin bound to surfaces such as membranes or a fibrin(ogen) clot. Fibrin-bound thrombin represents a reservoir of active thrombin that can exacerbate both venous and arterial thrombosis by generating more fibrin locally or when released by fibrinolysis. Fibrin-bound thrombin may also activate factor XIII, the transglutaminase that crosslinks fibrin and thrombin-activatable fibrinolysis inhibitor.
Fibrin-bound thrombin is inaccessible to heparin/heparin cofactor II inactivation, but it is susceptible to dermatan sulfate/heparin cofactor II inactivation. As opposed to heparin, dermatan sulfate specifically activates heparin cofactor II inhibition of thrombin. However, hemorrhage is also a side effect of utilizing dermatan sulfate as an antithrombotic agent.
Accordingly, there is a need in the art for anticoagulating and antithrombotic agents with high activity and low incidents of side effects. The present invention fulfills this longstanding need.